DESCRIPTION: Experiments of this proposal will test the hypothesis that 17 beta-estradiol preserves normal endothelial control of vascular tone in hypercholesterolemia by limiting modification of low-density lipoproteins and production of superoxide, thereby, preserving the actions of endothelium-derived relaxing factor. The investigation of the antioxidant effects of estrogen at physiological concentrations are proposed. The first specific aim is to characterize the effect of endogenous estrogens, estrogen replacement and estrogen withdrawal on the responses of the coronary arteries in animals fed a hypercholesterolemic diet using standard organ chamber techniques. The second specific aim will be to investigate how estrogens modify serum and membrane lipoproteins. The third specific aim will be to investigate the cellular mechanisms responsible for estrogen mediated modulation of coronary arterial responses including oxidation of low-density lipoprotein and production of superoxide.